Indicators of the atherogenic lipoprotein phenotype measured with density gradient ultracentrifugation predict changes in carotid intima-media thickness in men and women

Figures & data

Table 1 Baseline demographic and clinical characteristics of subjects according to tertiles of posterior wall common carotid artery intima media thickness progression

Parameter	CIMT progression <−0.0035 mm (n = 36)	CIMT progression −0.0035 and <0.0214 mm (n = 37)	CIMT progression ≥0.0214 mm (n = 37)	P-valuea
Mean (SEM)
Age, years	61.0 (8.8)	60.4 (8.3)	60.8 (6.7)	0.790b
BMI, kg/m^2	27.5 (4.9)	29.3 (3.4)	29.1 (4.9)	0.136
Systolic BP, mmHg	131.1 (15.7)	127.8 (17.1)	130.8 (21.6)	0.955
Diastolic BP, mmHg	70.5 (12.3)	70.7 (9.3)	72.2 (8.9)	0.480
Fasting glucose, mg/dL	92.1 (8.2)	95.0 (9.0)	97.7 (9.2)	0.006b
Vitamin D (25-OH), ng/mL	19.4 (12.6, 29.7)	19.1 (13.7, 26.3)	23.5 (16.7, 31.4)	0.150b
Baseline CIMT, mm	0.84 (0.11)	0.75 (0.07)	0.73 (0.06)	<0.001b
Framingham 10-yr riskc	7.7 (5.9)	7.8 (4.9)	9.8 (5.9)	0.063b
Number (%)
Men	18 (50.0)	23 (62.2)	21 (56.8)	0.577
Age intervals				0.573
≤64 years	22 (61.1)	24 (64.9)	26 (70.3)
≥65 years	14 (38.9)	13 (35.1)	11 (29.7)
Race/ethnicity				0.404
White	21 (58.3)	27 (73.0)	25 (67.6)
Black	10 (27.8)	7 (18.9)	9 (24.3)
Asian	2 (5.6)	3 (8.1)	1 (2.7)
Hispanic/latino	1 (2.8)	0 (0.0)	2 (5.4)
BMI ≥ 30 kg/m^2	10 (27.8)	15 (40.5)	15 (40.5)	0.426
Medication use
Antihypertensive	14 (38.9)	7 (18.9)	14 (37.8)	0.117
Aspirin	10 (27.8)	5 (13.5)	8 (21.6)	0.323
Lipid-alteringd	10 (27.8)	2 (5.4)	9 (24.3)	0.032
Major CHD risk factor
Smoker	5 (13.9)	7 (18.9)	8 (21.6)	0.686
BP ≥ 140/90 mmHg or use of antihypertensive agents	20 (55.6)	16 (43.2)	20 (54.1)	0.515
HDL-C < 40 mg/dL	18 (50.0)	21 (56.8)	27 (73.0)	0.119
Family history of CHD	4 (11.1)	1 (2.7)	1 (2.7)	0.190

a Notes: P-values for continuous variables were for the slope (test for trend) derived by linear regression analysis, and by chi-square test for categorical values;

b values were not normally distributed, and were ranked prior to the final analysis;

c 10-year % risk of a CHD event;

d of the 24 subjects taking lipid-altering medications, 17 were on a statin.

Abbreviations: BMI, body mass index; BP, blood pressure; CHD, coronary heart disease; CIMT, carotid artery intima media thickness; HDL-C, high-density lipoprotein cholesterol; SEM, standard error of the mean.

Table 2 Baseline density gradient ultracentrifugation lipid measurements according to tertiles of posterior wall carotid intima media thickness progression

Parameter (mg/dL except LDL peak time which is seconds)	CIMT progression <−0.0035 mm (n = 36)	CIMT progression −0.0035 and <0.0214 mm (n = 37)	CIMT progression ≥0.0214 mm (n = 37)	P-valuea
Mean (SEM) or median (IQL)
TC	156.3 (4.6)	158.7 (4.8)	165.8 (5.7)	0.181
Total LDL-Cb	97.2 (3.6)	99.4 (3.7)	106.2 (4.5)	0.107
“Real” LDL-Cb	78.8 (3.6)	80.7 (3.6)	86.3 (4.0)	0.156
LDL1+2-C	29.9 (19.1, 39.4)	30.2 (17.7, 38.2)	24.2 (17.5, 32.6)	0.115c
LDL3+4-C	47.7 (3.2)	49.5 (2.4)	59.3 (3.5)	0.008
Lp(a)-C	4.0 (3.0, 8.5)	5.0 (4.0, 7.0)	6.0 (4.0, 8.0)	0.301c
LDL peak time	115.6 (0.6)	114.6 (0.7)	112.5 (0.6)	0.001
IDL-C	12.0 (10.0, 14.0)	10.0 (10.0, 15.0)	12.0 (10.0, 17.0)	0.502c
Total HDL-C	39.0 (1.8)	37.7 (1.7)	34.9 (1.7)	0.095
HDL2-C	8.5 (6.0, 12.0)	9.0 (5.0, 11.0)	7.0 (6.0, 9.0)	0.028c
HDL3-C	29.5 (1.3)	29.1 (1.1)	27.3 (1.2)	0.188
Total VLDL-C	19.0 (15.0, 23.5)	18.0 (15.0, 23.0)	23.0 (18.0, 29.0)	0.010c
VLDL1+2-C	7.4 (5.5, 9.6)	6.8 (6.0, 9.6)	9.9 (7.3, 14.6)	0.002c
VLDL3-C	11.5 (10.0, 13.5)	11.0 (10.0, 13.0)	13.0 (11.0, 16.0)	0.022c
Non-HDL-C	117.2 (4.0)	121.0 (4.2)	130.9 (4.9)	0.028
TG	63.0 (43.0, 87.5)	70.0 (53.0, 101.0)	103.0 (72.0, 127.0)	<0.001c
Apo B DGU	81.5 (2.2)	84.3 (2.2)	91.3 (2.8)	0.005
Apo B immunoassay	79.5 (2.7)	82.0 (2.4)	91.7 (3.0)	0.002

a Notes: P-values derived by linear regression model analysis;

b total LDL-C = LDL_1+2+3+4-C+ Lp(a)-C + IDL-C and “Real” LDL-C = LDL_1+2+3+4-C;

c values were not normally distributed, and were ranked prior to the final analysis.

Abbreviations: Apo, apolipoprotein; CIMT, carotid intima media thickness; DGU, density gradient ultracentrifugation; HDL-C, high-density lipoprotein cholesterol; IDL-C, intermediate density lipoprotein cholesterol; IQL, interquartile limits; LDL-C, low-density lipoprotein cholesterol; Lp(a)-C, cholesterol carried by lipoprotein(a); SEM, standard error of the mean; TC, total cholesterol; TG, triglycerides; VLDL-C, very low density lipoprotein cholesterol.

Table 3 Linear regression analysis for progression rate (mm/year) after adjustment for baseline posterior wall carotid intima media thickness

Variable	Regression coefficient (SE)	P-value
TC	0.0000 (0.0001)	0.842
Total LDL-Ca	0.0001 (0.0001)	0.359
“Real” LDL-Ca	0.0001 (0.0001)	0.451
LDL1+2-C	−0.0001 (0.0001)	0.562
LDL3+4-C	0.0001 (0.0001)	0.147
Lp(a)-C	0.0000 (0.0001)	0.601
LDL peak time	−0.0002 (0.0001)	0.045
IDL-C	0.0001 (0.0001)	0.557
Total HDL-C	−0.0003 (0.0001)	0.001
HDL2-C	−0.0003 (0.0001)	0.005
HDL3-C	−0.0003 (0.0001)	0.003
Total VLDL-C	0.0002 (0.0001)	0.037
VLDL1+2-C	0.0002 (0.0001)	0.016
VLDL3-C	0.0002 (0.0001)	0.056
Non-HDL-C	0.0001 (0.0001)	0.173
TG	0.0002 (0.0001)	0.079
Apo B DGU	0.0001 (0.0001)	0.133
Apo B immunoassay	0.0002 (0.0001)	0.067

a Notes: Total LDL-C = LDL_1+2+3+4-C + Lp(a)-C + IDL-C and “Real” LDL-C = LDL_1+2+3+4-C.

Abbreviations: Apo, apolipoprotein; CIMT, carotid intima media thickness; DGU, density gradient ultracentrifugation; HDL-C, high-density lipoprotein cholesterol; IDL-C, intermediate density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Lp(a)-C, cholesterol carried by lipoprotein(a); SE, standard error; TC, total cholesterol; TG, triglycerides; VLDL-C, very low density lipoprotein cholesterol.